Glutaminase as a metabolic target of choice to counter acquired resistance to Palbociclib by colorectal cancer cells.

Several mechanisms of resistance of cancer cells to cyclin-dependent kinase inhibitors (CDKi) have been identified, including the upregulation of metabolic regulators such as glutaminase. However, whether such resistance mechanisms represent optimal targets has not been determined. Here, we have systematically analyzed metabolic reprogramming in colorectal cancer cells exposed to Palbociclib, a CDKi selectively targeting CDK4/6, or Telaglenastat, a selective glutaminase inhibitor.

Glutamine Modulates Expression and Function of Glucose 6-Phosphate Dehydrogenase via NRF2 in Colon Cancer Cells.

Nucleotide pools need to be constantly replenished in cancer cells to support cell proliferation. The synthesis of nucleotides requires glutamine and 5-phosphoribosyl-1-pyrophosphate produced from ribose-5-phosphate via the oxidative branch of the pentose phosphate pathway (ox-PPP). Both PPP and glutamine also play a key role in maintaining the redox status of cancer cells.